This invention relates to a process for preparing 2-ketogulonic acid, its alkyl esters and salts by the selective reduction of 2,5-diketogluconic acid, alkyl esters or salts thereof. 2-ketogulonic acid is useful as an intermediate for the preparation of ascorbic acid.
The complete reduction of 2,5-diketogluconic acid with an excess of sodium borohydride has been reported as part of a structural determination of the acid, see Agr. Biol. Chem. 28, 819 (1964), J. Biol. Chem. 204, 34 (1953) and Antonie Van Leeuwenhoeck 37, 185 (1971). The catalytic reduction of 2,5-diketogluconic acid using a Raney nickel catalyst and hydrogen gives a low yield of a mixture of 2-ketogluconic acid and 2-ketogulonic acid, with 2-ketogluconic acid being the major product, Agr. Biol. Chem. 28, 819 (1964). Applicant's copending U.S. Patent application Ser. No. 843,946 filed Dec. 10, 1977, U.S. Pat. No. 4,159,990, discloses a process for the reduction of a 2,5-diketogluconate with one equivalent of an alkali metal borohydride to form a mixture of 2-ketogulonic acid and 2-ketogluconic acid.
It has now been found that a 2,5-diketogluconate can be reduced with greater regioselectivity and stereoselectivity, thereby giving higher yields of the desired 2-ketogulonic acid for subsequent conversion to ascorbic acid, by use of an amine-borane reducing agent at a pH between about 2 and 7. Thus, for example yields of 2-ketogulonic acid and 2-ketogluconic acid of 94% or higher, with about 96% of the product mixture being the desired 2-ketogulonic acid, may be obtained by this process. These higher yields can be obtained without conducting the reduction reaction in the presence of a boron-complexing agent as is required for optimum yields in the alkali metal borohydride reduction. It has also been found that 2-ketogulonic acid formed by this process is not subject to further reduction, i.e., reduction of the 2-keto group, at a reasonable rate even in the presence of excess amine-borane reducing agent. The 2-keto group of 2-ketogulonic acid is, however, rapidly reduced by an alkali metal borohydride, resulting in less than optimum yields of 2-ketogulonic acid when formed by the alkali metal borohydride reduction of a 2,5-diketogluconate and precluding the use of excess alkali metal borohydride to increase rates of reduction and conversions of the 2,5-diketogluconate starting material. Further, the 2,5-diketogluconate is most stable under the acidic conditions employed in the present amine-borane reduction.